Process for the manufacture of alphahydroxy isobutyric acid



United States Patent ABSTRACT OF THE DISCLOSURE A tertiary butyl ester of isobutylene is oxidized to produce as the principal reaction product, alpha-hydroxyisobutyric acid. The oxidation is carried out in the presence of nitric acid or an oxide of nitrogen at a temperature of between about 0 and 100 C. The t-butyl ester of isobutylene is desirably of an acid which is a lower alkanoic acid or a mineral acid. Among the t-butyl esters of isobutylene which may be employed are the acetate, nitrate, chloride, propionate, oxalate, phosphate, etc.

. This application is a continuation of my copending application Ser. No. 435,702, filed Feb. 26, 1965, now abandoned, which is in turn a continuation of Ser. No. 184,514, filed Apr. 2, 1962, now abandoned, which is in turn a continuation-in-part of my earlier application Ser. No. 46,912, filed Aug. 2, 1960, now abandoned.

This invention relates to a novel process for producing alpha-hydroxyisobutyric acid from a t-butyl ester.

It is an important object of the present invention to provide an economical, nonhazardous process for producing alpha-hydroxyisobutyric acid.

It is another object of the present invention to provide an economical process for producing alpha-hydroxyisobutyric acid by oxidizing a t-butyl ester with nitric acid or an oxide of nitrogen, preferably dinitrogen tetroxide.

Other objects of the present invention will be apparent to those skilled in the art from reading the present specification.

As disclosed in Gardner et al. Patent No. 2,847,453 and Robertson et al. Patent No. 2,847,465, it is known that alpha olefins, such as isobutylene, may be oxidized to alpha hydroxy carboxylic acids, such as alpha-hydroxyisobutyric acid, by treatment with nitric acid alone, or by an oxide of nitrogen, such as dinitrogen tetroxide, either pure or in conjunction with nitric acid. The processes of these patents provide an economical integrated means of producing alpha-hydroxyisobutyric acid which is a valuable intermediate from which methacrylic acid or its esters may be obtained by methods described in the patents.

While the processes of the foregoing patents provide excellent results and yields of alpha-hydroxyisobutyric acid, in order to get the best yields it is necessary to carry out the processes at low temperatures and there is an explosion hazard involved. This increases the costs substantially, since expensive refrigeration equipment is required. Also, the reaction is highly exothermic, making it diflicult to control and prevent the temperature from increasing excessively.

It has been discovered in accordance with the present invention that alpha-hydroxyisobutyric acid may be economically and safely produced by oxidizing a t-butyl ester with nitric acid or an oxide of nitrogen, preferably dinitrogen tetroxide.

The process of the present invention may be carried out either in the absence of a solvent or in a reaction ice solvent such as nitric acid or a mixture of nitric and acetic acids, preferably the azeotrope, as disclosed in my earlier US. application, Ser. No. 46,912, filed Aug. 2, 1960. It is intended to incorporate by reference in its entirety the disclosure of my said US. patent application, Ser. No. 46,912. Other solvents may be employed, such as sulfuric acid or phosphoric acid, or other solvents of low pH.

The process of the invention can be carried out more advantageously when dinitrogen tetroxide is employed as the oxidizing agent, if the dinitrogen tetroxide is dissolved in a substantially azeotropic mixture of acetic acid and nitric acid. Such a maximum boiling azeotropic mixture comprises approximately 66 mole percent of glacial acetic acid and 33 mole percent of nitric acid (2:1 molar ratio), although substantial variations in the molar ratios of acetic to nitric acids are permissible without impairing the advantageous results obtained. Thus, for example, molar ratios of acetic to nitric acids of between about 0.5 and 3 to 1, and preferably between about 1.5 and 3 to 1, are satisfactory. Small amounts of water, desirably less than about 15% and preferably less than 5%, may also be present without having an adverse effect.

While varying proportions of dinitrogen tetroxide and an isobutylene ester may be employed when dinitrogen tetroxide is employed as the sole oxidizing agent, it is desirable to employ at least one mole of dinitrogen tetroxide for each mole of the ester. Most desirably a ratio of at least 2 to 1 is employed. When the reaction is carried out at the higher temperatures in the presence of a nitric acid containing solvent, the addition of small amounts of dinitrogen tetroxide will generate additional amounts of dinitrogen tetroxide to carry out the oxidation reaction.

When nitric acid is used as the oxidizing agent, the conversion of a t-butyl ester will take place when at least the stoichiometric amount of nitric acid required for the reaction is employed, i.e., the mole ratio of nitric acid to isobutylene ester is at least 1:1. However, better results have been obtained when the nitric acid is used in excess over the stoichiometric amount needed to convert t-butyl ester to alpha-hydroxyisobutyric acid. It is preferable, therefore, to maintain the mole ratio of nitric acid to a t-butyl ester on the order of 2:1 or higher. The nitric acid in the present invention not only reacts with the t-butyl ester but also serves as a solvent for the reaction.

The reaction can be initiated either by adding a little dinitrogen tetroxide (N 0 at the start of the reaction, or by heating a small portion of the reaction mixture itself to a temperature on the order of 50 C. so as to reduce the nitric acid sufficiently to form a little dinitrogen tetroxide. However, the use of initiators is not required.

The process may be carried out at realtively low temperatures, such as 0 C., up to as high as 50 to C. and even C. One of the advantages of the process of the present invention over similar processes employing isobutylene per se as the starting material is that higher temperatures such as 50 to 75 C. may be employed without incurring an explosion hazard. In addition to freedom from explosion, the process obviates the need for expensive refrigeration equipment in the process.

Another important advantage of the process of the present invention is that it is less exothermic and is easier to control than processes employing isobutylene as the starting material. It is described in the literature that isobutylene reacts reversibly in the presence of acids to make t-butyl compounds (US. Patent 2,380,350; J.A.C.S. volume 56, p. 1230 [1934]). It is my interpretation that by the present invention a controlled concentration of isobutylene is regenerated in the oxidation mixture.

Although I do not wish to be bound by this interpretation, it is supported by the fact that the present invention provides the same product spectrum as does the oxidation of isobutylene by nitric acid or dinitrogen tetroxide. However, the exothermic character is diminished, control of temperature is easier and suitable reaction temperatures are higher.

Various isobutylene esters may be employed, including those of organic carboxylic acids and inorganic acids. These include t-butyl sulfate, chloride, nitrate, phosphate, acetate, propionate and oxalate. These esters can be produced by reacting isobutylene with the acid of the ester, such as by dissolving isobutylene in the acid. Also, they may be produced by esterifying t-butyl alcohol with the desired acid, in accordance with known methods, or the t-butyl alcohol can be esterified and oxidized concurrently.

A typical preparation of t-butyl esters can be made as follows. In any convenient manner, 0.5 mole of isobutylene is mixed, either as gas or as liquid, with a solution of 1.15 moles of acetic acid, 0.77 mole of nitric acid and 0.24 mole of water. This results in the formation of 0.27 mole of t-butyl nitrate, 0.09 mole f t-butyl acetate, and 0.14 mole of t-butyl alcohol. The resulting solution is suitable for oxidation to alpha-hydroxyisobutyric acid.

In order more clearly to disclose the nature of the present invention, the following examples illustrating the invention are disclosed. It should be understood, however, that this is done solely by Way of example, is intended neither to delineate the scope of the invention, nor limit the ambit of the appended claims.

EXAMPLE I A solution of 1.0 mole of isobutylene was made in 2.5 moles of nitric acid, 4.6 moles of acetic acid and 0.25 mole of water. This rapidly formed mixed t-butyl esters at ambient temperature. This solution was added during 30 minutes to a solution of 4.0 moles of dinitrogen tetroxide in 5.1 moles of nitric acid, 9.4 moles of acetic acid and 0.5 mole of water. The temperature was held at 35 C. during this time. Thereafter, the mixture was heated at 60 C. for an hour and at 80 C. for another hour. This produced a solution containing a 74% yield of recoverable alpha-hydroxyisobutyric acid which includes free alpha-hydroxyisobutyric acid and its acetate, nitrate, and dimer.

The yield can be increased to 78% by holding the" original mixture for as long as 6 hours at 35 C. before the treatment at the higher temperature.

EXAMPLE II A solution of t-butyl sulfate was made by adding 1.35 moles of t-butyl alcohol to 2.0 moles of 67% sulfuric acid in water. This esterification was accelerated by warming the mixture.

The oxidation was performed at 60 C. by adding the ester solution continuously over a period of one hour to 12 moles of 70% nitric acid in water. After the addition was complete, the mixture was held for four hours at 80 C. The product comprised 31% of the theoretical of alpha-hydroxyisobutyric acid and its esters.

EXAMPLE III A solution of 0.2 mole of t-butyl nitrate was made by dissolving isobutylene in 0.76 mole of 58% aqueous nitric acid. An additional separate 0.7 mole of 8% nitric acid was heated to 60 C. and two drops of liquid dinitrogen tetroxide was introduced to initiate reaction in the nitric .acid. The t-butyl nitrate solution prepared above was added at the bottom of the nitric acid containing the dinitrogen tetroxide. Temperature was controlled at 80 C. by the rate of addition. The reaction was complete in three hours. The yield of recoverable alpha-hydroxyisobutyric acid was 27% of theoretical.

EXAMPLE IV A t-butyl phosphate solution was made from 1.4 moles of t-butyl alcohol and 19 moles of 62% aqueous phosphoric acid. A solution of 12 moles of 70% nitric acid was heated to 60 C. and the t-butyl phosphate solution was added over a one-hour interval. The reaction temperature was kept in the range 55 to C. by the rate of addition. Finally the rnixture wasmaintained for two hours at C. At this point it contained a 29% yield of recoverable alpha hydroxyis'obutyric acid."

EXAMPLE V This run was performed by pumping each of two solutions simultaneously into a stirred, jacketed stainless steel reactor. Solution #1 contained dinitrogen tetroxide, solution #2 contained t-butyl esters of nitric .and acetic acids. Solvent for both solutions was a mixture of nitric acid, acetic acid and water in the mole ratio of 2.2/ 3.4/0.9. The t-butyl esters were prepared by dissolving isobutylene in this solvent. The temperature of reaction was maintained at 82 C. by circulating water from a constant temperature bath adjusted to keep 82 C. in the reactor. A pressure regulator on the outlet from the reactor kept the contents at 100 p.s.i.g. The feed was introduced at .033 reactor volume per minute. The composite feed contained esters corresponding to 1.0 mole of isobutylene, as well as 2.25 moles of dinitrogen tetroxide for each 2.2 moles of nitric acid.

A steady-state sample from this reactor was held for an hour at C. whereupon it was shown to contain 0.49 mole of recoverable alpha-hydroxyisobutyric acid for every mole of isobutylene used in the form of t-butyl esters.

EXAMPLE VI A 4.2 mole batch of purified t-butyl acetate was added slowly to a solution of 17.4 moles of dinitrogen tetroxide, 9 moles of nitric acid, 16.9 moles of acetic acid and 2.4 moles of water. The reaction mixture was held at 20 C. with external cooling during the addition. Thereafter the reaction heated itself to 60 C., where it was maintained for one hour. After an additional treatment of two hours at 80 C., the mixture contained a 55% yield of recoverable alphahydroxyisobutyric acid.

EXAMPLE VII By the use of the same technique and-quantities described in Example VI, 4.2 moles of t-butyl nitrate was oxidized to alpha-hydroxyisobutyric acid in 55% yield.

EXAMPLE VIII By the use of the same technique and quantities described in Example VI, 4.2 moles of t-butyl alcohol was oxidized to alpha-hydroxyisobutyric acidin 46% yield.

As is well known, dinitrogen tetroxide exists in an equilibrium mixture of the monomer, nitrogen dioxide (N0 and the dimer (N 0 The equilibrium concentration of the monomer is a function of temperature, as described in Inorganic Chemistry, F. Ephraim, 3rd English edition, (Nordman, New York) (1939), page 667. When. used in this specification and the claims, the. expression dinitrogen tetroxide is intended to include the equilibrium concentrationof the monomer at the temperature employed. 1

The terms and expressions which have been employed are used as terms of description and not of limitation,- and it is not intended, in the use of such terms and ex-.

pressions, to exclude any equivalents of the features shown and described or portions thereof, but it is recognized 1. A process of producing as a principal reaction product, alpha-hydroxyisobutyric acid, which comprises,

oxidizing a t-butyl ester of isobutylene and an acid selected from the class consisting of lower alkanoic acids and mineral acids with a member selected from the class consisting of nitric acid and an oxide of nitrogen at a temperature between about 0 and 100 C.

2. A process as defined by claim 1, wherein the oxide of nitrogen is dinitrogen tetroxide.

3. A process of producing as a principal reaction product, alpha-hydroxyisobutyric acid, which comprises oxidizing a t-butyl ester of isobutylene and an acid selected from the class consisting of hydrochloric, nitric, phosphoric, acetic, propionic and oxalic acids with a member selected from the class consisting of nitric acid and an oxide of nitrogen at a temperature between 0 and 100 C.

4. A process as defined by claim 1, wherein the tertiary butyl ester is oxidized by dinitrogen tetroxide in a reaction solvent comprising a mixture of acetic and nitric acids wherein the molar ratio of acetic to nitric acids in the reaction solvent is between about 0.5 and 3 to 1.

5. A process as defined by claim 1, wherein the reaction is carried out in an azeotropic mixture of acetic and nitric acids.

6. A process as defined by claim 1, wherein dinitrogen tetroxide is the oxidizing agent and is generated, in part, in the reaction mixture by the action of small amounts of dinitrogen tetroxide on nitric acid contained therein.

7. A process as defined by claim 1, wherein the t-butyl ester is t-butyl nitrate.

8. A process as defined by claim 1, wherein the t-butyl ester is t-butyl phosphate.

9. A process as defined by claim 1, wherein the t-butyl ester is t-butyl acetate.

10. A process as defined by claim 1, wherein the t-butyl ester is formed in situ and oxidized concurrently by addition of t-butyl alcohol to the system, which contains nitric acid.

References Cited UNITED STATES PATENTS 3,198,823 8/1965 Akabayashi et a1. 260-533 2,971,981 2/1961 Aries 260-535 2,847,465 8/1958 Robertson 266--533 2,847,453 8/1958 Gardner 260--533 2,380,350 7/1945 Willauer et a1. 260-677 3,284,494 11/1966 Schoenbrunn 260535 XR OTHER REFERENCES Clingman, In, et 211.: Industrial & Engineering Ohemistry, vol. 50, pp. 777-780 (5-1958).

Schoenb'runn et al.: Journal Am. Chemical Society, vol. 82, pp. 4915-8 (1960).

LORRAINE A. WEINBERGER, Primary Examiner.

A. P. HALLUIN, Assistant Examiner. 

